One of the earliest studies of blood irradiation therapy was published in 1981 by Russian scientists, i.e., Mishalkin, E., editor, “Application of direct laser irradiation in experimental and clinical heart surgery (in Russian),” Novosibirsk: Nauka. The studied technique required insertion of a cannula that contained a plastic laser catheter into a vein in the forearm of a human patient, and feeding the low intensity laser light into the blood stream through the cannula. This was an early mode of treatment of cardiovascular diseases, in which both the microcirculation and the rheological properties of blood were improved.
Later published studies further demonstrated that blood rheology can be improved particularly with green or blue wavelengths of laser light (see, Mi, et al., “A comparative study of 632.8 and 532 nm laser irradiation on some rheological factors in human blood in vitro,” Journal of Photochemistry and Photobiology, 74:1: 7-12 (2004); and Gasparyan, L, “Laser irradiation of the blood,” Laser Partner Clinixperience, 58 (2003)).
Later reported studies also suggested that it does not matter if the light energy is coherent (i.e., laser light), but that the light energy instead be of an effective wavelength and be delivered at the correct dosage. For example, incoherent red from a Light Emitting Diode (LED) is expected to perform as well as laser light to produce low-power laser clinical effects; and the primary difference between laser light and LED light is that the laser's coherent beam produces “speckles” of relatively high power density which can cause local heating of inhomogeneous tissues (see, Karu, T. I., “The Science of Low Power Laser Therapy,” Gordon and Breach Scientific Publications, London (1998)). Other studies/reports have described additional benefits and aspects of LLLT (see e.g., Michael R. Hamblin, “Mechanisms of Low Level Light Therapy,” (2008); Scott Roberts, “LED Light Therapy”; and Tiina Karu, “Action Spectra, Their Importance for Low Level Light Therapy”). The studies have also shown that use of 405-450 nm wavelengths (the violet-blue region of the spectrum) are effective with respect to cytochrome c-oxidase.
The studies have also shown that the basis for the effectiveness of the wavelengths of the LLLT relates to quantum mechanical theory (QMT), in that per QMT, light is composed of photons, the energy of which depends upon its wavelength. The photons of the light directed onto living tissue will either be absorbed or scattered, and only the photons that are absorbed may interact with the living tissue. The absorbed photons, typically for the red and NIR wavelengths, may interact in one of three ways—i) the energy of the photon may create heat; ii) the molecular absorption of a photon may result in emission of a different photon having a longer wavelength; or iii) the photon may trigger any one of a number of processes known as photochemistry, which is particularly relevant for the blood.
The normal circulating blood, i.e., blood containing non-aggregated red blood cells (RBCs), performs many important life functions in the mammalian body. Blood provides a supply of oxygen to living tissues via the hemoglobin internally carried by RBCs. Blood provides a supply of nutrients such as glucose, amino acids, and fatty acids. These nutrients are dissolved in the blood or are bound to plasma. Blood acts to remove waste products such as carbon dioxide, urea, and lactic acid. Blood performs diverse immunological functions, including the circulation of multiple kinds of white blood cells, as well as the detection and binding of foreign material by antibodies. Blood provides the cascade of proteins needed for blood clotting or coagulation as part of the body's self-repair mechanisms. Blood provides the entities for messenger functions, including the transport of hormones and the chemical signaling of tissue damage. Blood serves to regulate body pH via blood acidity. Blood regulates the core body temperature. Blood also performs many hydraulic (fluid mechanical) functions.
A blood sample from an unhealthy subject shows that his/her red blood cells may be joined together and form an aggregate, and the presence of such RBC aggregates creates “high viscosity” and a marked resistance to flow for the circulating blood in that individual. The aggregated RBCs in blood of such an unhealthy subject would form irregular clusters or masses of cells, causing at least some functional roles of blood to become severely compromised. It is therefore medically desirable and clinically therapeutic if such RBC aggregates in the circulating blood could be made to dissociate and disaggregate into separated and individual red blood cells.
The present invention is particularly configured to provide portable biostimulation using low level light therapy (LLLT), also known as photobiomodulation, at particularly beneficial wavelengths, using particular power levels and pulsing at a duty cycle for the application of the necessary amount of energy, at an optimal delivery location to achieve in-vivo reversal of red blood cell aggregation, without invading the tissues or organs of the living subject—a clinical result which leads to a lower blood viscosity and improved blood circulation. In one embodiment of the present invention, light energy is configured for location-specific delivery using a bracelet to irradiate arterial and venous blood located beneath the skin of the wrist/forearm (e.g., the radial and ulnar arteries). The present invention may also be advantageously utilized upon any other region of the body, and thus may be similarly adapted and directed to use on the neck, the torso, or any other portion of any of a person's limbs, including, but not limited to, the foot, ankle, calf muscle, knee, thigh, etc. In addition the components described herein may also be utilized in a helmet-like/helmet worn device to be worn on the person's head for treatment thereto. Therefore, any description hereinafter that is described with reference to the wrist region, is not intended to be limited to such applicability.
The vasculature lying adjacent to the wrist is particularly receptive to biostimulation. The quantity of blood flow at that location is quite large; and the rate of blood flow is routinely higher per unit area of tissue in comparison to the rate of blood flow into other anatomic locales such as the brain, or the liver, or the muscles. Therefore, the therapeutic benefits of such irradiation light therapy are quickly spread throughout the whole body via the blood circulation system.
The benefits of the particular red wavelength(s) of light used herein are: a) the wavelength(s) are readily absorbed by the mitochondria and stimulatory therein; b) the wavelength(s) also stimulate growth; c) the wavelength(s) do not penetrate deep below the skin surface and into the tissue below; d) the wavelength(s) are non-thermal, and therefore do not create any burns.
The benefits of the infrared wavelength(s) used herein are: a) the wavelength(s) are absorbed through the cell walls (acting differently between cells) and therefore cell response is more wavelength specific, responding differently to different wavelengths; and b) the wavelength(s) are more penetrative through the tissue, for treatment through intact skin, possibly being more stimulatory than red light.
The wavelength(s) in or near the start of the ultraviolet spectrum used herein are particularly beneficial, as it has been shown that both the light frequencies in the red and infrared range most typically used in LLLT as well as wavelengths in the violet and blue range, may influence the localized production and release of nitric oxide, and may stimulate vasodilation through the effect of the nitric oxide on cyclic guanosine monophosphate (cGMP), which is a cyclic nucleotide derived from guanosine triphosphate (GTP), which acts as a messenger, and is regarded as an activation mechanism for intracellular protein kinases. The bracelet (or any other form) of the present invention is therefore designed to be effective for patients who would benefit from increased localized nitric oxide availability, and thus may include wavelengths at and/or in the ultraviolet spectrum, and also blue wavelengths of light. Also, Tiina Karu notes the following in “Action Spectra, Their Importance for Low Level Light Therapy”):                “Recall that in the wavelength range 310-500 nm, a maximum stimulating effect was obtained with a radiation dose one order of magnitude less than in the longer-wave spectral range (3, 4). This is noted in FIG. 3 by Curves 1 and 2. The bands in the action spectrum were identified in (20, and reviewed in 9) by analogy with the metal-ligand systems absorption spectra characteristic of this spectral range. The regions 400-450 nm and 620-680 nm are characterized by the bands pertaining to complexes with charge transfer in a metal-ligand system, and within 760-830 nm, these are d-d transitions in metals (21-23). The region 400-420 nm is typical of π-π* transitions in a porphyrin ring (24).”        
Research has shown that to be efficacious, the intensity of the light applied to treat injuries at a skin surface may preferably be between 4 mW/cm2 and 15 mW/cm2, which would require, assuming 5% penetration through the skin, application of light at an intensity of 80 mW/cm2 at the low end (net penetration of 4 mW/cm2), and an intensity of 300 mW/cm2 at the high end (net penetration of 15 mW/cm2). It has furthermore been found that apart from the deleterious effect of heating, that long duration pulses may not be optimal for treatment, i.e., pulses such as 50 microsecond on and 250 microsecond off (less than a 50% duty cycle), with an average intensity of 30 mW/cm2 may desirably provide a total of 180 mW/cm2 during each 50 microsecond cycle.
The Mammalian body temperature is normally controlled by an internal autonomic regulatory system referred to herein as the thermoregulatory system. Normally, when body and or environmental temperatures are high, dilation of certain blood vessels favors high blood flow to the noted heat exchange surfaces, thus increasing heat loss to the environment and temperature reduction in the deep body core region. Conversely, as environmental and/or body temperatures fall, vasoconstriction reduces blood flow to these surfaces and minimizes heat loss to the environment.
However, there are situations in which it is desirable to manipulate the transfer of heat across skin surfaces, to modulate the body temperature, where particular applications may include the treatment of normal and abnormal physiological conditions, e.g., disease and/or discomfort, particularly for alleviation or treatment of hot flashes, treatment of exercise or work induced hyperthermia, treatment of stroke, treatment of cystic fibrosis symptoms, treatment of multiple sclerosis symptoms, and the like. By “treatment” it is meant that it results in at least an alleviation in one or more of the symptoms associated with the condition being treated, e.g. a reduction in discomfort, amelioration or elimination of symptoms, etc. Core body cooling, (or heating) may be useful not only for therapeutic treatment regimens, but also as a component of improving athletic or industrial performance. Where the herein disclosed device is also used for body temperature regulation during a workout, it may serve: to increase exercise efficiency and capacity; to extend exercise times including longer time to reach 50% strength reduction; to help the user to achieve a higher peak force in resistance training; to lower creatine kinase blood levels (muscle damage index); to naturally and safely stimulate the production of body and brain chemicals that increase physical energy and to attain a sense of well-being derived from the release of certain neurotransmitters such as serotonin and dopamine.
Therefore, another aspect of the present invention is its ability to manipulate the transfer of heat across skin surfaces to modulate body temperatures. The device may include a cooling apparatus, such as a cold pack, an ice pack, or a thermoelectric cooling unit, positioned in proximity to the skin of the wearer of the device. The device may be configured to provide thermal pulses to the wearer's skin surface (e.g., a 33% duty cycle @120 seconds—30 second on and 90 seconds off, or instead, may preferably be a 120 second cycle, with 20 seconds on and 100 seconds off).
In some cases, the average rate of the initial temperature adjustment may be greater in magnitude than the average rate of the return temperature adjustment. Also, the thermal pulse may include a first temperature adjustment at the region of the at least one thermoelectric unit adjacent the skin surface from a first temperature to a second temperature at a first average rate of between about 0.1° C./sec and about 10.0° C./sec, and a second temperature adjustment from the second temperature to a third temperature at a second average rate of between about 0.1° C./sec and about 10.0° C./sec, wherein a difference in magnitude between the first temperature and the third temperature may be less than 25% of a difference in magnitude between the first temperature and the second temperature.